Variant chr6-29942863-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_002116.8(HLA-A):c.180C>T(p.Phe60Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0454 in 1,499,998 control chromosomes in the GnomAD database, including 5,692 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

Frequency

Genomes: 𝑓 0.065 ( 754 hom., cov: 17)

Exomes 𝑓: 0.044 ( 4938 hom. )

Consequence

HLA-A
NM_002116.8 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.339

Variant links:

Genes affected

HLA-A (HGNC:4931): (major histocompatibility complex, class I, A) HLA-A belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen so that they can be recognized by cytotoxic T cells. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. More than 6000 HLA-A alleles have been described. The HLA system plays an important role in the occurrence and outcome of infectious diseases, including those caused by the malaria parasite, the human immunodeficiency virus (HIV), and the severe acute respiratory syndrome coronavirus (SARS-CoV). The structural spike and the nucleocapsid proteins of the novel coronavirus SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19), are reported to contain multiple Class I epitopes with predicted HLA restrictions. Individual HLA genetic variation may help explain different immune responses to a virus across a population.[provided by RefSeq, Aug 2020]

HLA-A links:

ENSG00000227766 (HGNC:):

ENSG00000227766 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP7

Synonymous conserved (PhyloP=0.339 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-A	NM_002116.8 link	c.180C>T	p.Phe60Phe	synonymous_variant	2/8	ENST00000376809.10	NP_002107.3	P04439-1B1PKY1B2R7U3
LOC124901298	XR_007059541.1 link	n.813+1918G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-A	ENST00000376809.10 link	c.180C>T	p.Phe60Phe	synonymous_variant	2/8	6	NM_002116.8	ENSP00000366005.5		P04439-1

Frequencies

GnomAD3 genomes

AF:

0.0646

AC:

7342

AN:

113684

Hom.:

750

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0912

Gnomad AMI

AF:

0.0890

Gnomad AMR

AF:

0.0590

Gnomad ASJ

AF:

0.0515

Gnomad EAS

AF:

0.00931

Gnomad SAS

AF:

0.0422

Gnomad FIN

AF:

0.0509

Gnomad MID

AF:

0.0397

Gnomad NFE

AF:

0.0577

Gnomad OTH

AF:

0.0612

GnomAD3 exomes

AF:

0.0599

AC:

14987

AN:

250200

Hom.:

489

AF XY:

0.0602

AC XY:

8148

AN XY:

135452

show subpopulations

Gnomad AFR exome

AF:

0.0995

Gnomad AMR exome

AF:

0.0566

Gnomad ASJ exome

AF:

0.0659

Gnomad EAS exome

AF:

0.0118

Gnomad SAS exome

AF:

0.0463

Gnomad FIN exome

AF:

0.0450

Gnomad NFE exome

AF:

0.0685

Gnomad OTH exome

AF:

0.0700

GnomAD4 exome

AF:

0.0439

AC:

60787

AN:

1386216

Hom.:

4938

Cov.:

AF XY:

0.0442

AC XY:

30479

AN XY:

689992

show subpopulations

Gnomad4 AFR exome

AF:

0.0854

Gnomad4 AMR exome

AF:

0.0383

Gnomad4 ASJ exome

AF:

0.0383

Gnomad4 EAS exome

AF:

0.00389

Gnomad4 SAS exome

AF:

0.0408

Gnomad4 FIN exome

AF:

0.0452

Gnomad4 NFE exome

AF:

0.0442

Gnomad4 OTH exome

AF:

0.0477

GnomAD4 genome

AF:

0.0647

AC:

7357

AN:

113782

Hom.:

754

Cov.:

AF XY:

0.0642

AC XY:

3530

AN XY:

54984

show subpopulations

Gnomad4 AFR

AF:

0.0914

Gnomad4 AMR

AF:

0.0589

Gnomad4 ASJ

AF:

0.0515

Gnomad4 EAS

AF:

0.00934

Gnomad4 SAS

AF:

0.0424

Gnomad4 FIN

AF:

0.0509

Gnomad4 NFE

AF:

0.0577

Gnomad4 OTH

AF:

0.0610

Alfa

AF:

0.0549

Hom.:

EpiCase

AF:

0.0738

EpiControl

AF:

0.0785

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over